NEUROIMAGING CORE PROJECT SUMMARY A major focus of the Wisconsin ADRC research agenda is multi-disciplinary translational neuroscience in humans with evidence of AD pathology with or without clinical features. In-vivo neuroimaging assessments, including new tau and amyloid imaging, and sophisticated analytic techniques are increasingly being utilized or sought by our investigators to gain further insights about the neurobiology of AD. The NeuroImaging Core was created to provide necessary infrastructure and resources for investigators to successfully implement imaging outcomes in an efficient manner. The Core reduces duplication of effort and resources, while at the same time maximizing the possibilities of collaboration and the leveraging of data across ADRC affiliated projects through standardization of select scan modalities/sequences. The Core has experienced extensive utilization and growth that exceeded projections resulting in support for over 45 funded projects, the majority were funded federally. This occurred largely by emphasizing support of new faculty and faculty who were not imaging experts per se, but nevertheless desired to enhance the significance and impact of their studies by incorporating state of the art imaging outcomes. The Core now proposes to add [F18]THK5351 tau imaging and [C11]PiB amyloid PET imaging for 300 participants. The original Specific Aims are: 1) To provide imaging support for the ADRC cohorts (MRI) and support the imaging needs in Project 2. 2) To provide imaging informatics support for ADRC-affiliated projects including tools for cataloging and interacting with imaging data in a project specific manner. 3) Make available the latest advanced PET and MRI imaging methods and data analysis capabilities to ADRC affiliated projects. 4) Provide training to investigators and staff in the ADRC and University at large on neuroimaging methods and analysis techniques pertaining to neuro-disorders. We also provide pre- and post-award consultation to investigators who are implementing/planning imaging studies, and assist in grant preparation, study design, and startup. The major goals of this supplemental proposal are to 1) Describe the spatial patterns of tau and amyloid across stages of AD, and identify those spatial pre- dementia disease profiles most associated with subsequent decline. 2) Determine the concordance between CSF metrics of AD pathology and tau and amyloid imaging. 3) To completely integrate amyloid and tau imaging information into our center's infrastructure, process, and data sharing initiatives. This award will significantly enhance the overall impact of the center by establishing crucial tau and amyloid molecular imaging endophenotypes. The field has suffered from a lack of clarity on preclinical AD, because we have not had the tools to spatially characterize amyloid plaque and NFTs. This project represents a unique opportunity to examine the earliest determinants of AD progression, which is a central scientific theme of the Wisconsin ADRC. The unique data collected will be made available immediately to the research community.